rs1436207

Positions:

• chr10-50278773-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000395526.9(ASAH2):​c.-154+810T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 152,212 control chromosomes in the GnomAD database, including 551 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.050 (551 hom., cov: 31)
• Consequence: ASAH2 ENST00000395526.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

Genes affected

ASAH2 (HGNC:18860): (N-acylsphingosine amidohydrolase 2) Ceramidases (EC 3.5.1.23), such as ASAH2, catalyze hydrolysis of the N-acyl linkage of ceramide, a second messenger in a variety of cellular events, to produce sphingosine. Sphingosine exerts both mitogenic and apoptosis-inducing activities, and its phosphorylated form functions as an intra- and intercellular second messenger (see MIM 603730) (Mitsutake et al., 2001 [PubMed 11328816]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASAH2	ENST00000395526.9	c.-154+810T>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7597 AN: 152092 Hom.: 543 Cov.: 31

Gnomad AFR AF: 0.0831

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00923

Gnomad OTH AF: 0.0516

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0502 AC: 7639 AN: 152212 Hom.: 551 Cov.: 31 AF XY: 0.0546 AC XY: 4065 AN XY: 74414

Gnomad4 AFR AF: 0.0839

Gnomad4 AMR AF: 0.0350

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0317

Gnomad4 NFE AF: 0.00923

Gnomad4 OTH AF: 0.0543

Alfa AF: 0.0323 Hom.: 29

Bravo AF: 0.0524

Asia WGS AF: 0.237 AC: 820 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1436207; hg19: chr10-52038533;